I wanted to stimulate some discussion regarding a recent article (and
corresponding News and Views) in Nature. Reference Gu et al., Nature 421,
63-66, and 31-32. Following excerpts (first two paragraphs followed by the
final paragraph of both articles) highlight the topic:

Original Article:
"Deleting a gene in an organism often has little phenotypic effect, owing to
two mechanisms of compensation. The first is the existence of duplicate
genes: that is, the loss of function in one copy can be compensated by the
other copy or copies. The second mechanism of compensation stems from
alternative metabolic pathways, regulatory networks, and so on. The relative
importance of the two mechanisms has not been investigated except for a
limited study, which suggested that the role of duplicate genes in
compensation is negligible. The availability of fitness data for a nearly
complete set of single-gene-deletion mutants of the Saccharomyces cerevisiae
genome has enabled us to carry out a genome-wide evaluation of the role of
duplicate genes in genetic robustness against null mutations. Here we show
that there is a significantly higher probability of functional compensation
for a duplicate gene than for a singleton, a high correlation between the
frequency of compensation and the sequence similarity of two duplicates, and
a higher probability of a severe fitness effect when the duplicate copy that
is more highly expressed is deleted. We estimate that in S. cerevisiae at
least a quarter of those gene deletions that have no phenotype are
compensated by duplicate genes.

No correlation was found between the sequence similarity of duplicate genes
and the fitness effect of a null mutation in one of the two duplicates when
functional data from the yeast S. cerevisiae was analysed previously10. It
was therefore concluded that gene duplications contribute little to the
ability of an organism to withstand mutations (genetic robustness), although
they may be responsible for a small fraction of weak, null-mutation
phenotypes12. Because this conclusion was based on only 45 duplicate genes,
however, the issue deserves further investigation. Indeed, this conclusion
is not supported by a limited analysis of a third of the genes in the yeast
genome1 and is contrary to the general observation of relaxed selective
constraints after gene duplication.

Although our estimates are compatible with the view that interactions among
unrelated genes rather than duplicate genes are the main cause of genetic
robustness against mutations10, 18, two additional factors need to be
considered. First, because we have considered only five growth conditions,
it is possible that when a gene deletion showed no effect in any of these
conditions it was not due to compensation by other genes but was because the
gene deleted was not related to the growth conditions used. Intuitively,
when more growth conditions are studied, both the proportion of duplicate
genes and the proportion of singletons that show only a weak or no effect of
deletion on growth rate will decrease. Indeed, the two proportions were
70.9% and 49.2% when only the YPD growth condition was considered (data not
shown), but became 64.3% and 39.5% when the five growth conditions shown in
Fig. 1a were used. The decrease is larger for singletons than for duplicate
genes, probably because duplicate genes have on average a stronger overlap
in function than do singletons and so can compensate each other in a wider
range of conditions. For this reason, our lower bound of 23% for the
relative contribution of duplicate genes to compensation for null mutations
is likely to be an underestimate. Second, a singleton in this or other
studies could actually have one or more paralogues in the genome that cannot
be detected by the criteria used but still overlap in function. Thus, gene
duplication might be the ultimate origin of functional compensation for some
'singletons'. In conclusion, whether the contribution of gene duplication to
genetic robustness is really less important than interactions among
unrelated genes is an issue that remains to be resolved by further studies."

News and Views:
"Duplicated genes are common in genomes, perhaps because they provide
redundancy: if one copy is inactivated, the other can still work. A new
study quantifies the effects of deleting 'singletons' and duplicated genes
in yeast.

In fairy tales, things frequently come in twos: there are, for instance, two
witches ruling over different parts of the land of Oz, two ugly sisters
vying for the attention of Cinderella's prince, and so on and so on. And the
phenomenon of duplication is not restricted to stories. In eukaryotes
(loosely speaking, those organisms, such as humans, whose DNA is packaged
into cell nuclei), genomes seem to be far from optimally designed, in that
most stretches of DNA sequence do not code for proteins, and even those
small portions that do are often duplicated. Why do organisms tolerate such
apparent wastage? Gu and colleagues1 tackle this question on page 63 of this
issue, looking specifically at the effects of duplicated genes on the
'fitness' of individuals.

An important line of thinking about why duplicated genes might arise goes
back 30 years to Susumo Ohno2, who stated that "natural selection merely
modified while redundancy created". Ohno reasoned that gene (and even
genome) duplications are not a burden on the organism, but rather the raw
material for evolutionary diversification ó in other words, duplication
allows new gene functions to evolve. One copy of a gene can carry out the
original task while the duplicate becomes free to accumulate mutations,
possibly developing new functions and allowing the big steps in evolution to
occur. In today's era of wholesale genome sequencing, Ohno's hypothesis has
gained many new adherents through the recognition that duplicate genes are
abundant in most genomes and that significant portions of genomes are
repeated. But, in general, the actual effects of 'singletons' and duplicated
genes on evolutionary fitness ó that is, on roughly how well different
individuals fare compared with others in terms of reproduction ó have not
been well studied at the whole-genome level.

On the other side of the coin, gene duplicates appear to have another
important function: they can buffer the genome against environmental
perturbations and mutations, because if one copy of the gene is somehow
inactivated, another with the same or a similar function can be used
instead. Such genetic redundancy is a headache for researchers trying to
determine the role of a particular gene, because the standard technique of
knocking out that gene in an organism might not have a noticeable effect,
thanks to functional substitution by the duplicate. Gu et al.1 shed new
light on this issue.

We are only now beginning to comprehend just how malleable genomes are, and
also how resilient they are in the face of so much genetic perturbation; for
instance, rearrangements and duplications of chromosomal segments are also
commonplace8, 9. Gu et al.1 have provided the first estimate (23ñ59%) of the
contribution of duplicated genes to genetic robustness. This may be one
reason why duplicated genes do not diverge to produce pseudogenes, or 'die',
as quickly or as often as had been predicted on the basis of
population-genetics theory10. I would guess that the existence of multiple
gene functions and their recruitment into novel gene networks provide
another explanation. But more needs to be learned about the evolution of
gene networks, through comparisons of complete genome sequences and through
further functional-genomic analyses, before this question can be answered."

So a few offhand questions:

Can we really assess the genome and proclaim that it is filled with junk
(and "not optimally designed" as quoted from the News and Views article) in
light of this study?

Does the fact that duplicated genes contribute to genetic robustness support
the conclusion of design or evolution?

Taking this data into account does the presence of duplicated genes by
themselves indicate clearly that they must be products of evolution?

What does the fact that deleting one copy of a duplicate gene 12.4% of the
time causes leathality indicate about the purpose of duplicate genes?
Simply raw material for evolution, or perhaps requisite components of a
well-designed system needed for reasons not yet determined? Consider also
the comments concerning the growth conditions that the authors make in the
last paragraph of the original paper in regards to this question.